Multi-omics Study of Hypoxic-Ischemic Brain Injury After Cardiopulmonary Resuscitation in Swine.

IF 3.1 3区医学 Q2 CLINICAL NEUROLOGY Neurocritical Care Pub Date : 2025-02-01 Epub Date: 2024-06-27 DOI:10.1007/s12028-024-02038-7

Shuhang Yu, Jiefeng Xu, Chenghao Wu, Ying Zhu, Mengyuan Diao, Wei Hu

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Abstract

Background: Hypoxic-ischemic brain injury is a common cause of mortality after cardiac arrest (CA) and cardiopulmonary resuscitation; however, the specific underlying mechanisms are unclear. This study aimed to explore postresuscitation changes based on multi-omics profiling.

Methods: A CA swine model was established, and the neurological function was assessed at 24 h after resuscitation, followed by euthanizing animals. Their fecal, blood, and hippocampus samples were collected to analyze gut microbiota, metabolomics, and transcriptomics.

Results: The 16S ribosomal DNA sequencing showed that the microbiota composition and diversity changed after resuscitation, in which the abundance of Akkermansia and Muribaculaceae_unclassified increased while the abundance of Bifidobacterium and Romboutsia decreased. A relationship was observed between CA-related microbes and metabolites via integrated analysis of gut microbiota and metabolomics, in which Escherichia-Shigella was positively correlated with glycine. Combined metabolomics and transcriptomics analysis showed that glycine was positively correlated with genes involved in apoptosis, interleukin-17, mitogen-activated protein kinases, nuclear factor kappa B, and Toll-like receptor signal pathways.

Conclusions: Our results provided novel insight into the mechanism of hypoxic-ischemic brain injury after resuscitation, which is envisaged to help identify potential diagnostic and therapeutic markers.

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猪心肺复苏后缺氧缺血性脑损伤的多组学研究

背景：缺氧缺血性脑损伤是导致心脏骤停（CA）和心肺复苏后死亡的常见原因；然而，具体的潜在机制尚不清楚。本研究旨在基于多组学分析探讨复苏后的变化：方法：建立 CA 猪模型，评估复苏后 24 小时的神经功能，然后将动物安乐死。收集其粪便、血液和海马样本，分析肠道微生物群、代谢组学和转录组学：结果：16S核糖体DNA测序显示，复苏后微生物群的组成和多样性发生了变化，其中Akkermansia和Muribaculaceae_unclassified的丰度增加，而双歧杆菌和Romboutsia的丰度下降。通过对肠道微生物群和代谢组学的综合分析，观察到了CA相关微生物与代谢物之间的关系，其中志贺氏菌与甘氨酸呈正相关。代谢组学和转录组学的综合分析表明，甘氨酸与涉及细胞凋亡、白细胞介素-17、丝裂原活化蛋白激酶、核因子卡巴B和Toll样受体信号通路的基因呈正相关：我们的研究结果为了解复苏后缺氧缺血性脑损伤的机制提供了新的视角，有望帮助确定潜在的诊断和治疗标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurocritical Care 医学-临床神经学

CiteScore

7.40

自引率

8.60%

发文量

221

审稿时长

4-8 weeks

期刊介绍： Neurocritical Care is a peer reviewed scientific publication whose major goal is to disseminate new knowledge on all aspects of acute neurological care. It is directed towards neurosurgeons, neuro-intensivists, neurologists, anesthesiologists, emergency physicians, and critical care nurses treating patients with urgent neurologic disorders. These are conditions that may potentially evolve rapidly and could need immediate medical or surgical intervention. Neurocritical Care provides a comprehensive overview of current developments in intensive care neurology, neurosurgery and neuroanesthesia and includes information about new therapeutic avenues and technological innovations. Neurocritical Care is the official journal of the Neurocritical Care Society.